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C Jorgensen

Publications and source records attributed to C Jorgensen.

108 records · Page 6Linked to original sources
PubMedDate not supplied

Rheumatoid arthritis associated with high levels of immunoglobulin a: clinical and biological characteristics.

We measured the serum immunoglobulins in 191 patients with rheumatoid arthritis (RA) over an 8-month period, looking for a relationship between high IgA levels, disease activity, and clinical and biological features. Twenty-nine patients with a polyclonal hyperimmunoglobulin A (IgA) (15.2%) above 5 g/l constituted group A. A control group of 29 randomized RA patients with normal IgA levels was studied over the same period (group B). The mean serum IgA concentration was significantly elevated in group A: 6.6 +/- 1.8 g/l versus 2.8 +/- 0.9 g/l in group B (p < 0.01). In group A, microscopic haematuria occurred in 20.7% of the cases, as against 3.4% from group B (p < 0.05). Furthermore, the incidence of unilateral sacroiliitis and of arthritis of the distal interphalangeal joints was significantly increased in group A (41.4% and 34.5%, respectively) against 6.9% and 3.4% in group B (p < 0.01) and this correlated with a high IgA serum level (p < 0.01). On the other hand, neither disease activity nor the biological parameters of inflammation were influenced by the level of IgA. Patients with RA associated with high levels of IgA are characterized by a significant increase in the incidence of distal interphalangeal arthritis, unilateral sacroiliitis and microscopic haematuria. These clinical and biological features could define a distinct subgroup of patients with RA.

Adult↗
PubMedDate not supplied

Visceral leishmaniasis infection in a rheumatoid arthritis patient treated with infliximab.

Anti-TNFalpha strategies can result in significant clinical benefits in rheumatoid arthritis (RA), but with an increased rate of opportunistic infections. Visceral leishmaniasis (VL) is a severe disease that can develop in immunocompromised hosts, principally in HIV patients. VL in RA patients treated with TNFalpha antagonists is an extremely rare event, and only one case has been described. Here we report a case of VL, occurring after 9 infusions of infliximab in association with azathioprine, in a patient who developed blood cytopenia, fluctuant fever, and splenomegaly.

Antibodies, Monoclonal↗
PubMedDate not supplied

Regulation of synovial cell proliferation and prostaglandin E2 production by combined action of cytokines.

To study the causes of synovitis in rheumatoid arthritis (RA), we have analyzed the effect of several cytokines known to be secreted in RA joints, on synovial cell proliferation and prostaglandin E2 (PGE2) production. Recombinant interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) stimulated moderately the DNA synthesis and markedly the production of PGE2. Interferon-gamma (IFN-gamma) was often mitogenic but never induced PGE2 secretion. The association of IL-1-beta and TNF-alpha showed an additive effect on both parameters, whereas addition of IFN-gamma to either monokine reduced the proliferation and increased PGE2 release. Incubation with a crude T cell supernatant or a mixture of cytokines including IL-1-beta, TNF-alpha and IFN-gamma enhanced synovial cell growth and PGE2 production as compared to the effect elicited by each single cytokine. In contrast, interleukin-2 (IL-2) down regulated the synovial cell activation induced by the combined action of the three other cytokines. Taken together, our findings indicate that synovial cell proliferation is weakly stimulated, reaching a two-fold increase over background levels, whatever cytokines are used. Furthermore, proliferation can vary independently of PGE2 production. Nevertheless, the monokines IL-1-beta and TNF-alpha both exert agonistic effects on synovial cell activation, thus contributing to cartilage damage in RA, whereas IFN-gamma, IL-6 or IL-2 may rather play a regulatory role.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Correlation between methotrexate pharmacokinetic parameters, and clinical and biological status in rheumatoid arthritis patients.

OBJECTIVE: To determine the correlation between the pharmacokinetic (PK) parameters of methotrexate (MTX), clinical status and laboratory test results in rheumatoid arthritis (RA) patients. METHODS: 22 patients (4 M/18F, mean age: 50 +/- 12 years, mean duration of RA: 8.5 +/- 6.5 years, mean duration on MTX: 8 +/- 10 months) were included in a prospective study. The mean dose of MTX administered was 6 +/- 0.7 mg/m2 of body area/week. No patient received any nonsteroidal antiinflammatory drug (NSAID). Blood and urine samples were collected over 24 hours (9 blood samples). The MTX concentrations were assayed by fluorescence polarization immunoassay. Clinical parameters (Ritchie articular index, morning stiffness, joint pain count, joint swelling count), hematological, liver and renal function tests, and ESR were recorded. Correlations between the patients' PK parameters, laboratory tests and clinical status were carried out using Pearson's correlation coefficient test. RESULTS: A significant correlation was observed between the Ritchie articular index, morning stiffness and the area under the curve (p = 0.009 and p = 0.026, respectively). No correlation was found with the other parameters. CONCLUSION: These results suggest that when the patient's disease activity is higher, the AUC becomes more important, reflecting a greater body exposure to MTX.

Adult↗
PubMedDate not supplied

Growth factor activity of IL-6 in the synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines. METHODS: The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA: RESULTS: We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts. CONCLUSIONS: These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.

Adult↗
PubMedDate not supplied

Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis.

The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.

Animals↗
PubMedDate not supplied

Endocarditis associated with ANCA.

We report the case of a patient exhibiting subacute bacterial endocarditis (SEB) associated with vasculitis and signs of nephritis. C-ANCA were present at high titer. This observation suggests that ANCA may be associated with vascular injury in SEB.

Aged↗
PubMedDate not supplied

Serum levels of secretory IgA and in vitro production of IgA in rheumatoid arthritis.

Twenty-three per cent of rheumatoid arthritis (RA) patients show an increase of serum IgA concentrations. To determine the role of mucous-associated lymphoid tissue (MALT) in the elevation of serum IgA in RA, we studied the serum secretory-IgA (s-IgA) in 63 RA patients and in 30 healthy controls. We also analysed the secretion of circulating B cells producing IgA, which is known to reflect mucous tissue activity, in a subgroup of 15 patients with increased serum IgA concentrations, and in control patients. The mean s-IgA in the RA patients was 0.046 mg/ml +/- 0.064, versus 0.002 +/- 0.004 mg/ml in controls (not significant). Active disease defined by clinical criteria was associated with an increase in serum s-IgA (p < 0.001). Furthermore, in a subgroup of RA patients with high serum IgA levels, we found an increase in in vitro IgA production by circulating blood lymphocytes (17.39 +/- 15.2 micrograms/ml), versus RA patients with normal serum IgA levels or controls (p < 0.001). These results were not modified by LPS or PWM. Our results further support the hypothesis of primary MALT activation following environmental antigenic stimulation in RA patients.

Adult↗
PubMedDate not supplied

Sensitivity of magnetic resonance imaging of the wrist in very early rheumatoid arthritis.

The aim of this study was to evaluate magnetic resonance images (MRI) of soft tissue abnormalities in the wrist of RA patients in the early stage of the disease. We performed magnetic resonance imaging of the wrist in 15 patients with early rheumatoid arthritis according to ACR criteria, of less than 10 months duration (mean duration 4.8 months). None of the patients had carpal bone erosions on standard radiography. MRI demonstrated abnormality of the soft tissue in 13 of the 15 cases. On coronal MRI, the sites of involvement of the synovitis were the recess of the distal ulnar (9 pts.), the distal radioulnar joint (4 pts.) and the radiocarpal joint (7 pts.). On axial MRI, tendon sheath effusion of the digital flexor was present in 3 patients. Carpal bone lacunae were present in only 4 patients. Disease activity was not associated with the extent of the synovitis on wrist MRI. Our study suggests that MRI is a sensitive method for the detection of synovitis in early RA.

Adolescent↗
PubMedDate not supplied

Autoimmunity. Insights provided by the SCID mouse model.

CB17 SCID mice have severe combined immunodeficiency as a result of a mutation on chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair. Because VDJ rearrangement does not occur, the humoral and cellular immune systems fail to mature. SCID mice do not reject human cells. They have been used to study the development of human tumors, human hematopoiesis and humoral responses in antibody-dependent organ-specific autoimmune diseases and in systemic lupus erythematosus. Studies involving grafting of synovial membrane under the renal capsule or in the subcutaneous tissue of SCID mice have provided information on the cells involved in the pathogenesis of rheumatoid arthritis. SCID mice have also been used to study adhesion molecules that play a role in the recruitment of lymphocytes in rheumatoid synovial tissue. The SCID mouse model provides new means of investigating immunologic treatments for rheumatoid arthritis.

Animals↗
PubMedDate not supplied

IgA isotype rheumatoid factor in rheumatoid arthritis: clinical implications.

OBJECTIVES: To study the clinical, biological and radiological characteristics of RA with a predominant increase of IgA isotype rheumatoid factor (IgA-RF) over IgM-RF. METHODS: The presence of IgA-RF was determined by a sandwich-type ELISA with an antibody against the human IgA used to capture the immunoglobulin. Associated RF activity was revealed with a peroxidase-conjugated human IgG Fc fragment. Forty-nine RA patients were studied, of whom 19 had an increase in IgA-RF (38%). The control group comprised 30 RA patients without IgA-RF. RESULTS: None of the patients had isolated IgA-RF. In the selected 19 RA patients, the OD of IgA-RF (0.971 +/- 0.62 U) was higher than the IgM-RF (mean OD: 0.675 +/- 0.522 U). A statistically significant correlation was found between IgA-RF and IgM-RF (r = 0.64, p < 0.0001). No correlation was noted between the IgA concentration and the IgA-RF titer. The two groups were comparable for age, disease duration, sex ratio and previous DMARD use. We observed that patients with RA associated with increased IgA-RF more often had the sicca syndrome, but no other extra-articular features. RA patients with IgA RF also had more erosive disease: the mean Larsen score at the hand and wrist was 76 (SD = 68) versus 54 (SD = 60) in the controls, p < 0.02. Replacement surgery for the hip or knee was necessary in 47% of the RA patients with IgA-RF, versus 13% in the controls, p < 0.01. No association of IgA-RF with disease activity was noted. CONCLUSION: Our study showed that RA patients with a predominant increase of IgA-RF had a more erosive disease and a high frequency of associated sicca syndrome.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Kinetics of prolactin release in rheumatoid arthritis.

OBJECTIVE: To study the dynamics of pituitary prolactin secretion in RA, and its association with the HLA DR4 status in patients. METHODS: TRH stimulation of the pituitary secretion of PRL was performed in 23 RA patients and 8 control subjects, all of whom were post-menopausal women. Hormone concentrations were assessed by radioimmunoassay. RESULTS: Basal prolactin concentrations were higher in RA patients compared to controls (579 +/- 80 mu UI/ml versus 187 +/- 47, (p < 0.01). An increase in the prolactin response to TRH at 30 min (2257 +/- 218 mu UI/l versus 1074 +/- 207, p < 0.005), independent of disease activity, was observed in the RA patients. In DR4+ RA patients, we observed a higher PRL peak at 60 min. (3913 +/- 506 mu UI/ml versus 2120 +/- 443, p < 0.01), and an increased residual value at 120 min compared to DR4- RA patients. The area under the curve of the PRL response was also increased in DR4+ RA patients, suggesting higher PRL secretion compared to DR4- RA patients. CONCLUSION: In female, post-menopausal RA patients an alteration in pituitary prolactin release, not linked to disease activity, can be observed. In DR4+ RA patients, the overall prolactin secretion reflected by the AUC is increased compared to DR4- patients. These results suggest a dysregulation of the pituitary response in RA.

Aged↗
PubMedDate not supplied

Vasculitis and psoriatic arthritis associated with Down's syndrome.

Only a few observations of inflammatory arthritis have been associated with Down's syndrome. We report a case of severe erosive, peripheral and axial psoriatic arthritis associated with cutaneous vasculitis in a 24-year old man with trisomy 21. A long standing remission of vasculitis and arthritis was achieved with corticoid and azathioprine treatment. The relationship between chromosomal abnormalities and synovial proliferation is further discussed.

Adult↗
PubMedDate not supplied

Association of methotrexate and corticosteroids in the treatment of patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether the association of methotrexate (MTX) and corticosteroids introduced concomitantly is more effective than MTX alone in patients with rheumatoid arthritis (RA). METHODS: Twenty-eight RA patients (group 1) were treated with MTX (mean dose: 10 +/- 1.4 mg/week) and corticosteroids (mean dose: 14.9 +/- 5.6 mg/day, range: 5-25) introduced concomitantly, and were compared to 251 RA patients (group 2) treated with MTX alone (mean dose: 9.8 +/-1.5 mg/week). Variations in the clinical (number of swollen and painful joints, morning stiffness, Ritchie's articular index), biological (ESR, CRP), and radiological parameters were studied. Remission was defined according to Pinals' criteria. At baseline, there were no significant differences between the two groups, except for a greater number of swollen and painful joints in group 1 (p = 0.03 and p = 0.01, respectively). The total MTX dose and the duration of treatment (26 +/- 21.8 months in group 1 versus 33.5 +/- 27.2) months in group 2) did not differ between the two groups. RESULTS: We noted a more marked reduction in the number of swollen and the number of painful joints in group 1 (p = 0.03). No differences were noted for the other clinical and biological parameters. The proportion of patients fulfilling Pinals' remission criteria was higher in group 1 (25% versus 10.1% in group 2, p = 0.04). The steroid dosage could be significantly reduced in group 1 (-3.4 +/- 6.1 mg/day, p = 0.05) and corticosteroids were stopped in 11 patients. The frequency and type of side effects, as well as the frequency and reasons leading to MTX withdrawal, did not significantly differ between the two groups. CONCLUSION: The association of MTX and corticosteroids seems to bring about a greater improvement in the different clinical activity parameters of RA than MTX alone, without any significant increase in the frequency of side effects. These results need to be confirmed in larger scale prospective studies.

Antirheumatic Agents↗
PubMedDate not supplied

Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients.

OBJECTIVE: To assess the efficacy and toxicity profile of methotrexate (MTX) as the initial second-line disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). METHODS: This was an observational retrospective cohort study comparing 28 patients who were treated with MTX as the first DMARD (MTX cases) and 55 matched patients treated with MTX after other DMARDs (MTX controls). RESULTS: The follow-up time was identical in the two groups: 19.4 +/- 14 months (2-56) for the MTX cases and 21.8 +/- 15.3 months (3-87) for MTX controls (NS). MTX efficacy was the same in the two groups, except for a higher incidence of remission in the MTX cases (8/28, 28.6% versus 5/55, 9.1%, p = 0.028). The toxicity profiles, frequencies, and reasons for MTX withdrawals were similar in the two groups. CONCLUSION: The results obtained in this study suggest a benefit from MTX prescribed as an initial second-line agent in the treatment of RA, but studies involving a larger number of patients are needed.

Adult↗